Abstract:
:Hypoxia-inducible factors (HIFs) are critical regulators of the cellular response to hypoxia. Despite their established roles in normal physiology and numerous pathologies, the molecular mechanisms by which they control gene expression remain poorly understood. We report here a conserved role for the TIP60 complex as a HIF1 transcriptional cofactor in Drosophila and human cells. TIP60 (KAT5) is required for HIF1-dependent gene expression in fly cells and embryos and colorectal cancer cells. HIF1A interacts with and recruits TIP60 to chromatin. TIP60 is dispensable for HIF1A association with its target genes but is required for HIF1A-dependent chromatin modification and RNA polymerase II activation in hypoxia. In human cells, global analysis of HIF1A-dependent gene activity reveals that most HIF1A targets require either TIP60, the CDK8-Mediator complex, or both as coactivators for full expression in hypoxia. Thus, HIF1A employs functionally diverse cofactors to regulate different subsets of genes within its transcriptional program.
journal_name
Cell Repjournal_title
Cell reportsauthors
Perez-Perri JI,Dengler VL,Audetat KA,Pandey A,Bonner EA,Urh M,Mendez J,Daniels DL,Wappner P,Galbraith MD,Espinosa JMdoi
10.1016/j.celrep.2016.05.082subject
Has Abstractpub_date
2016-06-28 00:00:00pages
37-47issue
1issn
2211-1247pii
S2211-1247(16)30695-7journal_volume
16pub_type
杂志文章相关文献
Cell Reports文献大全abstract::Over 80% of pancreatic ductal adenocarcinoma (PDA) patients are diagnosed with non-resectable late-stage disease that lacks effective neoadjuvant therapies. Stereotactic body radiation therapy (SBRT) has shown promise as an emerging neoadjuvant approach for treating PDA, and here, we report that its combination with l...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.08.095
更新日期:2019-10-08 00:00:00
abstract::Glioblastoma multiforme (GBM) is among the most aggressive of human cancers. Although differentiation therapy has been proposed as a potential approach to treat GBM, the mechanisms of induced differentiation remain poorly defined. Here, we established an induced differentiation model of GBM using cAMP activators that ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.12.037
更新日期:2017-01-10 00:00:00
abstract::Quiescence is a fundamental property of adult stem cells. Recent evidence indicates that quiescence is not a default state but requires active signaling that prevents accidental or untimely activation of stem cells. The calcitonin receptor (CalcR) is critical for sustaining quiescence in muscle satellite (stem) cells ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.10.057
更新日期:2019-11-19 00:00:00
abstract::Elevated levels of the free amino acid L-tryptophan (L-Trp) trigger expression of the tryptophanase tnaCAB operon in E. coli. Activation depends on tryptophan-dependent ribosomal stalling during translation of the upstream TnaC peptide. Here, we present a cryoelectron microscopy (cryo-EM) reconstruction at 3.8 Å resol...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.09.011
更新日期:2014-10-23 00:00:00
abstract::Experimental large-scale screens for drug repositioning are limited by restriction to in vitro conditions and lack of applicability to real human conditions. Here, we developed an in silico screen in human in vivo conditions using a reference of single gene mutations' non-tissue-specific "core transcriptome signatures...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.09.031
更新日期:2018-10-09 00:00:00
abstract::The subgranular zone (SGZ) of the adult hippocampus contains a pool of quiescent neural progenitor cells (QNPs) that are capable of entering the cell cycle and producing newborn neurons. The mechanisms that control the timing and extent of adult neurogenesis are not well understood. Here, we show that QNPs of the adul...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.10.037
更新日期:2013-11-27 00:00:00
abstract::Metabolically healthy obese subjects display preserved insulin sensitivity and a beneficial white adipose tissue gene expression pattern. However, this observation stems from fasting studies when insulin levels are low. We investigated adipose gene expression by 5'Cap-mRNA sequencing in 17 healthy non-obese (NO), 21 i...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.07.070
更新日期:2016-08-30 00:00:00
abstract::Despite recent progress in engineering native trimeric HIV-1 envelope glycoprotein (Env) mimics as vaccine candidates, Env trimers often induce vaccine-matched neutralizing antibody (NAb) responses. Understanding the specificities of autologous NAb responses and the underlying molecular mechanisms restricting the neut...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.03.039
更新日期:2019-04-09 00:00:00
abstract::Alzheimer's disease (AD) is associated with the intracellular aggregation of hyperphosphorylated tau and the accumulation of β-amyloid in the neocortex. We use transgenic mice harboring human tau (rTg4510) and amyloid precursor protein (J20) mutations to investigate transcriptional changes associated with the progress...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.01.063
更新日期:2020-02-11 00:00:00
abstract::Several pattern-recognition receptors sense HIV-1 replication products and induce type I interferon (IFN-I) production under specific experimental conditions. However, it is thought that viral sensing and IFN induction are virtually absent in the main target cells of HIV-1 in vivo. Here, we show that activated CD4+ T ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.09.023
更新日期:2016-10-04 00:00:00
abstract::To survive adverse and ever-changing environmental conditions, an organism must be able to adapt. It has long been established that the cellular reaction to stress includes the upregulation of genes coding for specific stress-responsive factors. In the present study, we demonstrate that during the early steps of the h...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.11.019
更新日期:2013-12-12 00:00:00
abstract::Information gained during goal pursuit motivates adaptive behavior. The anterior cingulate cortex (ACC) supports adaptive behavior, but how ACC signals are translated into motivational signals remains unclear. Rats with implants in the ACC and ventral tegmental area (VTA), a dopaminergic brain area implicated in motiv...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.05.062
更新日期:2017-06-13 00:00:00
abstract::Transport of RNAs to dendrites occurs in neuronal RNA granules, which allows local synthesis of specific proteins at active synapses on demand, thereby contributing to learning and memory. To gain insight into the machinery controlling dendritic mRNA localization and translation, we established a stringent protocol to...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.11.023
更新日期:2013-12-26 00:00:00
abstract::The ultimate goal of protein design is to introduce new biological activity. We propose a computational approach for designing functional antibodies by focusing on functional epitopes, integrating large-scale statistical analysis with multiple structural models. Machine learning is used to analyze these models and pre...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.10.081
更新日期:2018-11-20 00:00:00
abstract::Kinase inhibitors represent the backbone of targeted cancer therapy, yet only a limited number of oncogenic drivers are directly druggable. By interrogating the activity of 1,505 kinase inhibitors, we found that BRD4-NUT-rearranged NUT midline carcinoma (NMC) cells are specifically killed by CDK9 inhibition (CDK9i) an...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.08.082
更新日期:2017-09-19 00:00:00
abstract::Attempts to generate functional blood cells from human pluripotent stem cells (hPSCs) remain largely unsuccessful, mainly due to the lack of understanding of the regulatory network of human hematopoiesis. In this study, we identified leucine-rich-repeat-containing G-protein-coupled receptor 4 (LGR4) as an essential re...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107600
更新日期:2020-05-05 00:00:00
abstract::In Drosophila, it is thought that peptidoglycan recognition proteins (PGRPs) SA and LC structurally discriminate between bacterial peptidoglycans with lysine (Lys) or diaminopimelic (DAP) acid, respectively, thus inducing differential antimicrobial transcription response. Here, we find that accessibility to PG at the ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.04.103
更新日期:2019-05-21 00:00:00
abstract::In response to DNA double-strand breaks (DSBs), H2AX is rapidly phosphorylated at Ser139 to promote DSB repair. Here we show that H2AX is rapidly stabilized in response to DSBs to efficiently generate γH2AX foci. This mechanism operated even in quiescent cells that barely expressed H2AX. H2AX stabilization resulted fr...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.11.054
更新日期:2015-12-29 00:00:00
abstract::Cell growth is coupled to cell-cycle progression in mitotically proliferating mammalian cells, but the underlying molecular mechanisms are not well understood. CyclinD-Cdk4/6 is known to phosphorylate RB to promote S-phase entry, but recent work suggests they have additional functions. We show here that CyclinD-Cdk4/6...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.03.068
更新日期:2020-04-14 00:00:00
abstract::Chronic exposure to nicotine upregulates nicotinic acetylcholine receptors (nAChRs), and such upregulation is critical for the development of nicotine dependence in humans and animal models. However, how nicotine upregulates nAChRs is not well understood. Here, we identify a key role for microRNA in regulating nicotin...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.10.043
更新日期:2017-11-07 00:00:00
abstract::The onset of anaphase is triggered by activation of the anaphase-promoting complex/cyclosome (APC/C) following silencing of the spindle assembly checkpoint (SAC). APC/C triggers ubiquitination of Securin and Cyclin B, which leads to loss of sister chromatid cohesion and inactivation of Cyclin B/Cdk1, respectively. Thi...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.01.032
更新日期:2017-02-07 00:00:00
abstract::The rate at which genomes diverge during speciation is unknown, as are the physical dynamics of the process. Here, we compare full genome sequences of 32 butterflies, representing five species from a hybridizing Heliconius butterfly community, to examine genome-wide patterns of introgression and infer how divergence e...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.09.042
更新日期:2013-11-14 00:00:00
abstract::Transcriptional regulation of circadian rhythms is essential for lipid metabolic homeostasis, disruptions of which can lead to metabolic diseases. Whether N6-methyladenosine (m6A) mRNA methylation impacts circadian regulation of lipid metabolism is unclear. Here, we show m6A mRNA methylation oscillations in murine liv...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.10.068
更新日期:2018-11-13 00:00:00
abstract::Medium spiny neurons (MSNs) of mice show opposing activities upon the initiation of a food-seeking lever press task. Ventromedial striatal (VMS)-MSNs are inhibited but ventrolateral striatal (VLS)-MSNs are activated; these activities mediate action selection and action initiation, respectively. To understand what inpu...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107829
更新日期:2020-06-30 00:00:00
abstract::Cytoplasmic long non-coding RNAs have been shown to act at many different levels to control post-transcriptional gene expression, although their role in translational control is poorly understood. Here, we show that lnc-31, a non-coding RNA required for myoblast proliferation, promotes ROCK1 protein synthesis by stabi...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.03.101
更新日期:2018-04-17 00:00:00
abstract::In humans, Vγ9Vδ2 T cells respond to self and pathogen-associated, diphosphate-containing isoprenoids, also known as phosphoantigens (pAgs). However, activation and homeostasis of Vγ9Vδ2 T cells remain incompletely understood. Here, we show that pAgs induced expression of the ecto-ATPase CD39, which, however, not only...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.06.009
更新日期:2016-07-12 00:00:00
abstract::Kappa opioid receptors (KORs) are involved in a variety of aversive behavioral states, including anxiety. To date, a circuit-based mechanism for KOR-driven anxiety has not been described. Here, we show that activation of KORs inhibits glutamate release from basolateral amygdala (BLA) inputs to the bed nucleus of the s...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.02.069
更新日期:2016-03-29 00:00:00
abstract::The fossil record is widely informative about evolution, but fossils are not systematically used to study the evolution of stem-cell-driven renewal. Here, we examined evolution of the continuous growth (hypselodonty) of rodent molar teeth, which is fuelled by the presence of dental stem cells. We studied occurrences o...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.03.064
更新日期:2015-05-05 00:00:00
abstract::Maintaining organelle function in the face of stress is known to involve organelle-specific retrograde signaling. Using Caenorhabditis elegans, we present evidence of the existence of such retrograde signaling for peroxisomes, which we define as the peroxisomal retrograde signaling (PRS). Specifically, we show that pe...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108653
更新日期:2021-01-19 00:00:00
abstract::Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone involved in nutrient homeostasis. GIP receptor (GIPR) is constitutively internalized and returned to the plasma membrane, atypical behavior for a G-protein-coupled receptor (GPCR). GIP promotes GIPR downregulation from the plasma membrane by inh...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.11.050
更新日期:2016-12-13 00:00:00